A central problem in cancer research is determining the structure of membranes in normal and tumor cells. Conventional transmission and scanning electron microscopy investigation in a number of laboratories are contributing to our knowledge of cell surface topography, but it is clear that fresh approaches are also needed. The purpose of this research project is to develop and apply a new kind of microscopy specifically designed to examine chemical differences in cell surfaces and other membranes. This technique, photoelectron microscopy, utilizes differences in ionization potentials and electron quantum yields to visualize the biological surfaces. The escape depth of the electrons is extremely short, which permits mapping of membrane surfaces without interference from the cytoplasmic contents of the cell. The mechanism of contrast is entirely different from transmission and scanning electron microscopy, and it is possible to visualize different biochemical features. In previous grant periods, the feasibility of this approach has been experimentally verified, the first low magnification images ever seen of biologcal samples have been reported, and the three main variables (lateral resolution, depth resolution and contrast) have been examined. The main experimental thrust during this renewal period involves determining the operating performance of the new photoelectron microscope completed in July, 1976. A number of components will be completed for this instrument including the stigmator, camera system, preparation chamber and the addition of a fourth electrostatic lens boosting the direct instrument magnification from x8,000 to potentially x200,000. A number of mammalian cell surfaces will be examined, including, for example, the chick fibroblasts. In parallel with these studies, basic photoelectron quantum yields will be measured for a variety of isolated cell surface components. BIBLIOGRAPHIC REFERENCES: Dam, R.J., Rempfer, G.F. and O.H. Griffith, "Photoelectron Microscopy of Organic Surfaces: The Effect of Substrate Reflectivity", J. Appl. Phys. 47, 861-865 (1976). Griffith, O.H. and R.J. Dam, "Photoelectron Microscopy and Quantum Yields of Membrane Phospholipids", Proc. Electron Microscopy Soc. Amer. 34, 32-33 (1976).